1,541 research outputs found
Single-Molecule Super-Resolution Imaging of T-Cell Plasma Membrane CD4 Redistribution upon HIV-1 Binding
The first step of cellular entry for the human immunodeficiency virus type-1 (HIV-1) occurs
through the binding of its envelope protein (Env) with the plasma membrane receptor CD4 and
co-receptor CCR5 or CXCR4 on susceptible cells, primarily CD4+ T cells and macrophages. Although
there is considerable knowledge of the molecular interactions between Env and host cell receptors
that lead to successful fusion, the precise way in which HIV-1 receptors redistribute to sites of
virus binding at the nanoscale remains unknown. Here, we quantitatively examine changes in the
nanoscale organisation of CD4 on the surface of CD4+ T cells following HIV-1 binding. Using singlemolecule super-resolution imaging, we show that CD4 molecules are distributed mostly as either
individual molecules or small clusters of up to 4 molecules. Following virus binding, we observe
a local 3-to-10-fold increase in cluster diameter and molecule number for virus-associated CD4
clusters. Moreover, a similar but smaller magnitude reorganisation of CD4 was also observed with
recombinant gp120. For one of the first times, our results quantify the nanoscale CD4 reorganisation
triggered by HIV-1 on host CD4+ T cells. Our quantitative approach provides a robust methodology
for characterising the nanoscale organisation of plasma membrane receptors in general with the
potential to link spatial organisation to function
Skin prick testing in patients using beta-blockers: a retrospective analysis
<p>Abstract</p> <p>Rationale</p> <p>The use of beta-blockers is a relative contraindication in allergen skin testing yet there is a paucity of literature on adverse events in this circumstance. We examined a population of skin tested patients on beta-blockers to look for any adverse effects.</p> <p>Methods</p> <p>Charts from 2004-2008 in a single allergy clinic were reviewed for any patients taking a beta-blocker when skin tested. Data was examined for skin test reactivity, type of skin test, concomitant asthma diagnosis, allergens tested, and adverse events.</p> <p>Results</p> <p>One hundred and ninety-one patients were taking beta-blockers when skin testing occurred. Seventy-two patients had positive skin tests. No tests resulted in an adverse event.</p> <p>Conclusions</p> <p>This data demonstrates the relative safety of administrating of skin prick tests to patients on beta-blocker treatment. Larger prospective studies are needed to substantiate the findings of this study.</p
Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria
The similarity in the genetic regulation of
arthropod and vertebrate appendage formation has been
interpreted as the product of a plesiomorphic gene
network that was primitively involved in bilaterian
appendage development and co-opted to build appendages
(in modern phyla) that are not historically related
as structures. Data from lophotrochozoans are needed to
clarify the pervasiveness of plesiomorphic appendage forming
mechanisms. We assayed the expression of three
arthropod and vertebrate limb gene orthologs, Distal-less
(Dll), dachshund (dac), and optomotor blind (omb), in
direct-developing juveniles of the polychaete Neanthes
arenaceodentata. Parapodial Dll expression marks premorphogenetic
notopodia and neuropodia, becoming restricted
to the bases of notopodial cirri and to ventral
portions of neuropodia. In outgrowing cephalic appendages,
Dll activity is primarily restricted to proximal
domains. Dll expression is also prominent in the brain. dac
expression occurs in the brain, nerve cord ganglia, a pair
of pharyngeal ganglia, presumed interneurons linking a
pair of segmental nerves, and in newly differentiating
mesoderm. Domains of omb expression include the brain,
nerve cord ganglia, one pair of anterior cirri, presumed
precursors of dorsal musculature, and the same pharyngeal
ganglia and presumed interneurons that express dac.
Contrary to their roles in outgrowing arthropod and
vertebrate appendages, Dll, dac, and omb lack comparable
expression in Neanthes appendages, implying independent
evolution of annelid appendage development. We infer
that parapodia and arthropodia are not structurally or
mechanistically homologous (but their primordia might
be), that Dll’s ancestral bilaterian function was in sensory
and central nervous system differentiation, and that
locomotory appendages possibly evolved from sensory
outgrowths
Implicating Self-Control in the Mechanism by which Implementation Intentions Reduce Stress-Induced Unhealthy Eating: a Comment on O’Connor et al.
Adding anthropometric measures of regional adiposity to BMI improves prediction of cardiometabolic, inflammatory and adipokines profiles in youths: a cross-sectional study
Identifying bereaved subjects at risk of complicated grief: Predictive value of questionnaire items in a cohort study
<p>Abstract</p> <p>Background</p> <p>Bereavement is a condition which most people experience several times during their lives. A small but noteworthy proportion of bereaved individuals experience a syndrome of prolonged psychological distress in relation to bereavement. The aim of the study was to develop a clinical tool to identify bereaved individuals who had a prognosis of complicated grief and to propose a model for a screening tool to identify those at risk of complicated grief applicable among bereaved patients in general practice and palliative care.</p> <p>Methods</p> <p>We examined the responses of 276 newly bereaved individuals to a variety of standardised and ad hoc questionnaire items eight weeks post loss. Inventory of Complicated Grief (ICG-R) was used as a gold standard of distress at six months after bereavement. Receiver operating characteristic (ROC) curves analysis was performed for all scales and items regarding ICG-R score. Sensitivity, specificity and area under curve (AUC) were calculated for scales and items with the most promising ROC curve analyses.</p> <p>Results</p> <p>Beck's Depression Inventory (BDI) was the scale with the highest AUC (0.83) and adding a single item question ('Even while my relative was dying, I felt a sense of purpose in my life') gave a sensitivity of 80% and specificity of 75%. The positive/negative predictive values for this combination of questions were 70% and 85%, respectively. With this screening tool bereaved people could be categorized into three groups where group 1 had 7%, group 2 had 23% and group 3 had 64% propensity of suffering from complicated grief six months post loss.</p> <p>Conclusions</p> <p>This study shows that the BDI in combination with a single item question eight weeks post loss may be used for clinical screening for risk of developing complicated grief after six months. The feasibility and clinical implications of the screening tool has to be tested in a clinical setting.</p
Deletion of Munc18-1 in 5-HT Neurons Results in Rapid Degeneration of the 5-HT System and Early Postnatal Lethality
The serotonin (5-HT) system densely innervates many brain areas and is important for proper brain development. To specifically ablate the 5-HT system we generated mutant mice carrying a floxed Munc18-1 gene and Cre recombinase driven by the 5-HT-specific serotonin reuptake transporter (SERT) promoter. The majority of mutant mice died within a few days after birth. Immunohistochemical analysis of brains of these mice showed that initially 5-HT neurons are formed and the cortex is innervated with 5-HT projections. From embryonic day 16 onwards, however, 5-HT neurons started to degenerate and at postnatal day 2 hardly any 5-HT projections were present in the cortex. The 5-HT system of mice heterozygous for the floxed Munc18-1 allele was indistinguishable from control mice. These data show that deletion of Munc18-1 in 5-HT neurons results in rapid degeneration of the 5-HT system and suggests that the 5-HT system is important for postnatal survival
Learning Priors for Bayesian Computations in the Nervous System
Our nervous system continuously combines new information from our senses with information it has acquired throughout life. Numerous studies have found that human subjects manage this by integrating their observations with their previous experience (priors) in a way that is close to the statistical optimum. However, little is known about the way the nervous system acquires or learns priors. Here we present results from experiments where the underlying distribution of target locations in an estimation task was switched, manipulating the prior subjects should use. Our experimental design allowed us to measure a subject's evolving prior while they learned. We confirm that through extensive practice subjects learn the correct prior for the task. We found that subjects can rapidly learn the mean of a new prior while the variance is learned more slowly and with a variable learning rate. In addition, we found that a Bayesian inference model could predict the time course of the observed learning while offering an intuitive explanation for the findings. The evidence suggests the nervous system continuously updates its priors to enable efficient behavior
Luminescence Dating in Fluvial Settings: Overcoming the Challenge of Partial Bleaching
Optically stimulated luminescence (OSL) dating is a versatile technique that utilises the two most ubiquitous minerals on Earth (quartz or K-feldspar) for constraining the timing of sediment deposition. It has provided accurate ages in agreement with independent age control in many fluvial settings, but is often characterised by partial bleaching of individual grains. Partial bleaching can occur where sunlight exposure is limited and so only a portion of the grains in the sample was exposed to sunlight prior to burial, especially in sediment-laden, turbulent or deep water columns. OSL analysis on multiple grains can provide accurate ages for partially bleached sediments where the OSL signal intensity is dominated by a single brighter grain, but will overestimate the age where the OSL signal intensity is equally as bright (often typical of K-feldspar) or as dim (sometimes typical of quartz). In such settings, it is important to identify partial bleaching and the minimum dose population, preferably by analysing single grains, and applying the appropriate statistical age model to the dose population obtained for each sample. To determine accurate OSL ages using these age models, it is important to quantify the amount of scatter (or overdispersion) in the well-bleached part of the partially bleached dose distribution, which can vary between sediment samples depending upon the bedrock sources and transport histories of grains. Here, we discuss how the effects of partial bleaching can be easily identified and overcome to determine accurate ages. This discussion will therefore focus entirely on the burial dose determination for OSL dating, rather than the dose-rate, as only the burial doses are impacted by the effects of partial bleaching
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